Pharmacokinetics of Single and Multiple Doses of a New Antiallergic Drug, Cetirizine, and Examination of Its Safety

Pharmacokinetic studies and examination of safety on single and multiple oralintake of cetirizine, a new antiallergic drug, were performed in 37 healthy male adult Japanese volunteers (single dose: 15 subjects, multiple dose : 22 subjects, 4 of whomreceived placebo, age: 23-45 years).1) In the single-intake study (cetirizine: 2.5-30mg), the concentration of cetirizineplasma increased in a dose-dependent manner. When 10, 20 and 30mg of the drug wasgiven, the mean Cmax was 214.5, 438.1 and 679.2ng/ml with the mean Tmax of 1.44, 1.50and 2.20hr, respectively. The metabolite (ucb 026) in the plasma was detected in only afew cases and the level was very low, compared with the unchanged form. In the 10, 20and 30mg groups approximately 50% of the given doses was excreted in urine in theunchanged form by 24hr, but the metabolite was not detected in the urine.2) In the multiple-dose study, 20mg(once per day, 20mg×1 group: twice per day, 10mg×2group), 30mg(once per day, 30 mg×1group)or placebo was given for 7 days.On the first day and the 7th day, the mean Cmax was 547.8 and 624.5 ng/ml in the 20mg×1group, 272.7 and 424.2ng/ml in the 10mg×2group, and 852.7 and 832.7 ng/ml in the 30mg×1group, respectively. Simulation usin.g the parameters obtained on the first day ofthe multiple-dose study showed a constant plasma concentration of cetirizine from the2nd day after administration in the 20mg×1 and 30mg×1groups;this concentrationwas almost equivalent to the values obtained in the subsequent days. However, thesimulation did not correspond well with the actual values obtained in the 10mg×2group, this is probably due to the inability to measure the terminal phase. The metabolite inblood was detected on the 2nd day after administration and the level was nearly constanton 6 and 7th day. Urinary excretion of the unchanged form increased almost linearly to48-58% on the first day and 59-70% of the doses given on the 7th day in the three groups, but the metabolite was not detected in urine.3) There were no abnormal findings due to cetirizine in blood, biochemical andurinary examinations, nor physiological signs such as pulse, respiration, blood pressureor ECG in the single or multiple doses study. No subjective symptoms due to the drugwere observed in either study except for one subject who became slightly sleepy duringdays 1-3 after administration of 20mg.